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Although anti-PD-1 antibody monotherapy (PD-1) is commonly used to treat advanced acral melanoma (AM), its efficacy is limited. Further, data on the efficacy of PD-1 plus anti-CTLA-4 antibody (PD-1+CTLA-4) for the treatment of AM are limited. Therefore, we compared the efficacy of PD-1+CTLA-4 and PD-1 in the treatment of Japanese patients with advanced AM.This retrospective study evaluated patients with advanced AM who were treated with PD-1 or PD-1+CTLA-4 as first-line immunotherapy in 24 Japanese institutions between 2014 and 2020. Treatment efficacy focussing on the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was compared between the two groups.In total, 254 patients (palm and sole melanoma [PSM], n = 180; nail apparatus melanoma [NAM], n = 74) were included. Among the patients with PSM, the ORR (19% vs. 31%; P = 0.44), PFS (5.9 vs. 3.2 months; P = 0.74), and OS (23.1 vs. not reached; P = 0.55) did not differ significantly between the PD-1 and PD-1+CTLA-4 groups. Among the patients with NAM, the ORR (61% vs. 10%; P 0.001) was significantly higher and PFS was longer (6.4 vs. 3.8 months; P = 0.10) in the PD-1+CTLA-4 group than in the PD-1 group. Cox multivariate analysis demonstrated that PD-1+CTLA-4 is an independent predictor of a favourable PFS in patients with NAM (P = 0.002).The efficacy of PD-1+CTLA-4 is not superior to that of PD-1 for the treatment of advanced PSM. However, PD-1+CTLA-4 may be more efficacious than PD-1 for the treatment of advanced NAM.

Background Keloid lesions are characterized by mesenchymal cell proliferation and excessive extracellular matrix deposition. Previous microarray analyses have been performed to investigate the mechanism of keloid development. However, the molecular pathology that contributes to keloid development remains obscure. Aim To explore the underlying essential molecules of keloids using microarrays. Methods We performed microarray analyses of keloid and nonlesional skin tissues both in vivo and in vitro. Gene expression levels were compared between tissues and cells. Quantitative reverse transcription (qRT)-PCR and immunohistochemical staining were used to determine the expression levels of molecules of interest in keloid tissues. Results Several common molecules were upregulated in both keloid tissues and keloid-lesional fibroblasts. PTPRD and NTM were upregulated both in vivo and in vitro. The genes MDFI and ITGA4 were located at the centre of the gene coexpression network analysis using keloid tissues. qRT-PCR revealed significant expression levels of PTPRD and MDFI in keloid tissues. Immunopathological staining revealed that MDFI-positive cells, which have fibroblast characteristics, were located in the keloid-associated lymphoid tissue (KALT) portion of the keloid tissue. Conclusion Our gene expression profiles of keloids could distinguish the difference between lesional tissue and cultured lesional fibroblasts, and MDFI was found to be commonly expressed in both tissues and cells. Thus, MDFI-positive cells, which were located in the KALT, may play an important role in keloid pathogenesis and thus might be useful for in vitro keloid studies.

Lymphomatoid papulosis (LyP) is one of primary cutaneous CD30-positive large T-cell lymphoproliferative disorders (CD30 + PCLPD) that seldom arises in the oral region. We report here an extremely rare case of LyP arising on the lip. A 25-year-old female developed a painless mass on her right upper lip, which gradually grew and became painful. She visited her dermatologist who diagnosed it as herpes labialis and administered valacyclovir, but the lesion was unchanged. Then, she was referred to our department. At first visit, the mass was elastic, slightly hard, scarlet in color, and 15 mm in diameter. As T-cell lymphoma was initially diagnosed following incisional biopsy, we referred her to the Departments of Hematology and also Dermatology at our hospital. Bone marrow examination showed no neoplastic changes, and positron emission tomography-computed tomography revealed no other lesion except on the lip. Although new lesions appeared on her upper lip during the examinations, the lesions spontaneously disappeared without further treatment after the biopsy. The final diagnosis was CD30 + PCLPD pathologically and LyP clinically. No recurrence was found during the 10-month follow-up period.

Hand eczema is a major occupational disease, especially in medical workers, reducing their quality of life (QOL) and work productivity. Daily wearing of fabric gloves to prevent loss of moisture and lipids from the surface of the hands has been regarded as good in the management of hand eczema. However, limited evidence is available regarding the efficacy of moisturizing care with daily gloves on hand eczema. This pilot study was performed to evaluate the efficacy of moisturizing intervention with daily wearing of fabric gloves on skin barrier function, disease severity, and microbiome in health-care workers with hand eczema. Study 1: Nurses in the neonatal intensive care unit or growing care unit with and without hand eczema were recruited in the study. Subjects were instructed to apply moisturizer and wear two types of fabric gloves, common cotton gloves and moisturizing fabric gloves containing malate, for 4 weeks. Study 2: Physicians and health-care workers were recruited and instructed to wear a cotton glove on one hand at nighttime for 4 weeks. Disease severity, skin barrier function, QOL, and hand microbiome (Study 1) were evaluated. Study 1 found that daily wearing of both types of fabric gloves accompanied by use of topical moisturizers reduced the severity of hand eczema without changing the variation of microbiome. Study 2 found no apparent change between wearing and not wearing cotton gloves. In summary, topical moisturizer is of fundamental importance, and concomitant use of fabric gloves may merely enhance the efficacy of moisturizer in the management of hand eczema.

Background Immune checkpoint inhibitors (ICIs) have a lower efficacy in mucosal melanoma (MUM) than in cutaneous melanoma. The use of combination treatments with radiotherapy (RT) to improve the efficacy in MUM, however, requires further investigation. Methods We retrospectively evaluated 225 advanced MUM patients treated with anti-PD-1 monotherapy (PD1; 115) or anti-PD-1 + anti-CTLA-4 combination therapy (PD1+CTLA4; 42) with or without RT (56 and 12, respectively). Treatment efficacy was estimated by determining the objective response rate (ORR) and survival rate with the Kaplan–Meier analysis. Results The baseline characteristics between the two groups in each ICI cohort were similar, except for Eastern Cooperative Oncology Group performance status in the PD1 cohort. No significant differences in ORR, progression-free survival (PFS), and overall survival (OS) were observed between the PD1 alone and PD1+RT groups in the PD1 cohort (ORR 26% versus 27%, P > 0.99; median PFS 6.2 versus 6.8 months, P = 0.63; median OS 19.2 versus 23.1 months, P = 0.70) or between the PD1+CTLA alone and PD1+CTLA4+RT groups in the PD1+CTLA4 cohort (ORR 28% vs 25%, P = 0.62; median PFS 5.8 versus 3.5 months, P = 0.21; median OS 31.7 versus 19.8 months, P = 0.79). Cox multivariate analysis indicated that RT in addition to PD1 or PD1+CTLA4 did not have a positive impact on the PFS or OS. Conclusions A prolonged survival benefit with RT in combination with ICIs was not identified for advanced MUM patients, although RT may improve local control of the tumour and relieve local symptoms.

Background Adult T-cell leukemia–lymphoma (ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection and is known to exhibit cutaneous involvement in 50% or more patients. Few studies have evaluated the clinicopathological significance of programmed death-1 (PD-1) expression in the cutaneous lesions of ATL. Methods Skin biopsy specimens from 29 ATL patients with cutaneous lesions were evaluated regarding the clinicopathological feature, survival outcome, and PD-1 expression level on infilitrated CD3+CD4 + CD25+ cells. The optimal cut-off point of PD-1 expression for clinicopathological feature and outcome was determined as the value of the maximum Youden index by receiver operating characteristic (ROC) analysis. Results PD-1 was expressed broadly from zero to 90% on the skin biopsy specimens of the 29 patints, with the median value of 50%. The PD-1-expression level was significantly higher in the poorer-prognosis eruption group (nodulotumoral, erythrodermic and purpuric types) (P = 0.003), in the poorer histopathological infiltration patterns (diffuse and nodular) (P = 0.007), and in the poorer infiltrating cell-size group (large-sized cells) (P = 0.017) than in the corresponding group. ROC curve analyses showed that the optimal cut-off value for PD-1-expression level to predict the poorer-prognosis eruption, the poorer- histopathological infiltration pattern, the poorer infiltration cell size, and the poorer outcome (death) was 60%, 50%, 50%, and 80%, respectively. Patients with high PD-1 expression had a shorter median survival time than those with low PD-1 expression (18.2 months vs. 26.0 months), but the difference was not statistically significant. Conclusions ATL patients with cutaneous lesions in which PD-1 were highly expressed have more advanced dermatological and histopathological patterns and possibly worse survival than those with low PD-1 expression on cutaneous lesions. Further large-scale studies are warranted to verify these findings.

Background Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients. Patients and methods We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4. Results Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001). Conclusions First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events., Highlights • Anti-PD-1 plus anti-CTLA-4 antibody therapy (PD1 + CTLA4) is an option for patients with advanced mucosal melanoma (MCM). • Data on the efficacy of PD1 + CTLA4 compared with PD-1 monotherapy (PD1) for MCM, however, are limited. • We retrospectively analyzed data from 329 Japanese patients with advanced MCM treated with PD1 or PD1 + CTLA4. • No significant differences in objective response rate, progression-free survival, or overall survival were observed. • Immune-related adverse events resulting in treatment cessation were higher in the PD1 + CTLA4 group.

Nivolumab, an anti-PD-1 antibody, has been shown to be effective in many cancers, such as malignant melanoma and lung cancer; however, nivolumab therapy can result in pseudoprogression. Diffuse alveolar hemorrhage (DAH) is persistent or recurrent pulmonary hemorrhage as a result of drugs, autoimmune diseases, or infections. DAH with pseudoprogression during nivolumab administration has rarely been reported. Herein, we describe our experience with one such case. A 41-year-old woman exhibited bloody sputum and ground glass opacities in the lungs along with tumor growth during nivolumab therapy for multiple lung metastases of malignant melanoma. We diagnosed DAH with pseudoprogression as a result of nivolumab and administered steroid therapy. The DAH subsequently improved and the tumor shrank. This case illustrates that nivolumab can cause DAH with pseudoprogression, which can be controlled by steroid therapy. Thus, if bloody sputum and ground glass opacities in the lungs are observed with tumor growth during nivolumab administration, steroid therapy should be considered to control DAH with pseudoprogression.

Background: In 1968 in western Japan, polychlorinated biphenyl-contaminated “Kanemi rice oil” was used in cooking, causing food poisoning in many people. More than 50 years have passed since the Yusho incident, and although inflammatory disorders such as suppuration have been observed in Yusho patients, the etiology of this inflammation susceptibility remains obscure. Objectives: To investigate the mechanisms of susceptibility to inflammation in Yusho patients, peripheral immune cell fractions and concentrations of inflammatory cytokines were evaluated in blood samples collected from both Yusho patients and age-matched healthy subjects undergoing medical examination in Nagasaki. Methods: To exclude diagnostic uncertainty, serum levels of polychlorinated biphenyl (PCB), polychlorinated quarterphenyl (PCQ), and polychlorinated dibenzofuran (PCDF) were measured. Immune cell (e.g. natural killer and regulatory T cell) populations were analyzed by flow cytometry. Serum cytokines involved in immune cell activation were measured by ELISA. Results: The relative proportion of natural killer cells was higher in Yusho patients than in healthy subjects, while the proportion of regulatory T cells did not differ between groups. Serum concentrations of IL-36 and IFN-γ were significantly lower in Yusho patients than in healthy subjects. Conversely, serum cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which is a cytokine related to activated NK cells, was higher in Yusho patients than in healthy subjects and was positively correlated with PCDF blood levels. Conclusion: Increased numbers of NK cells in Yusho patients suggests that the innate immune response has been activated in Yusho patients. The seemingly paradoxical results for CTLA-4 and IFN-γ may reflect counterbalancing mechanisms preventing excessive NK cell activation. This dysregulation of innate immunity might contribute to the inflammation observed in Yusho patients., Environmental Research, 185, art.no.109415; 2020

Skin is a large organ that is susceptible to damage by external forces, chronic inflammation, and autoimmune reactions. In general, tissue damage causes alterations in both the configuration and type of cells in lesional skin. This phenomenon, called tissue remodeling, is a universal biological response elicited by programmed cell death, inflammation, immune disorders, and tumorigenic, tumor proliferative, and cytoreductive activity. During this process, changes in the components that comprise the extracellular matrix are required to provide an environment that facilitates tissue remodeling. Among these extracellular matrix components, periostin (a glycoprotein secreted predominantly by dermal fibroblasts) has attracted much attention. In normal skin, periostin localizes mainly in the papillary dermis and basement membrane of the epidermis. However, it is expressed at higher levels in the dermis of lesional skin of those with atopic dermatitis, scars, systemic/limited scleroderma, melanoma, and cutaneous T cell lymphoma; expression is also increased by damage caused by allergic/autoimmune responses. Furthermore, periostin induces processes that result in development of dermal fibrosis; it also activates or protracts the immune response. The aim of this review is to summarize recent knowledge about the role of periostin in the pathogenesis of dermatoses.

Skin is a large organ that is susceptible to damage by external forces, chronic inflammation, and autoimmune reactions. In general, tissue damage causes alterations in both the configuration and type of cells in lesional skin. This phenomenon, called tissue remodeling, is a universal biological response elicited by programmed cell death, inflammation, immune disorders, and tumorigenic, tumor proliferative, and cytoreductive activity. During this process, changes in the components that comprise the extracellular matrix are required to provide an environment that facilitates tissue remodeling. Among these extracellular matrix components, periostin (a glycoprotein secreted predominantly by dermal fibroblasts) has attracted much attention. In normal skin, periostin localizes mainly in the papillary dermis and basement membrane of the epidermis. However, it is expressed at higher levels in the dermis of lesional skin of those with atopic dermatitis, scars, systemic/limited scleroderma, melanoma, and cutaneous T cell lymphoma; expression is also increased by damage caused by allergic/autoimmune responses. Furthermore, periostin induces processes that result in development of dermal fibrosis; it also activates or protracts the immune response. The aim of this review is to summarize recent knowledge about the role of periostin in the pathogenesis of dermatoses.

Rubinstein-Taybi syndrome (RTS) is an autosomaldominant hereditary disease, which contains many skeletal and organ anomalies as well as mental retardation. Although high incidence of keloids in RTS is known, it is difficult to find a detailed report on the clinical features of keloids. In the following letter, we report an RTS patient fulfilling diagnostic criteria whosuffered from both keloids and pilomatricoma. We also performed a literature search, which identified the possible involvement of the Wnt/β-catenin signaling pathway in the pathogenesis of these two skin lesions.

Dioxin and dioxin-like compounds receptor (Ahr) mainly expressed on the surface of regulatory T (Treg) cell and Th17 cell could regulate immunological functions in the Yusho patients. We prospectively analyzed data obtained in a total of 56 cases of Yusho, which include patients identified ('Nintei' ) or non-identified ( 'Minintei') or identified as a family member, at the annual health check in 2014. The number of Treg cell showed lower among identified patients compared with non-identified group or family identified group (p = 0.4184 and p = 0.291, respectively). There was also a strong correlation between serum levels of neutral fat and the number of Treg cells (p = 0.0313). These results suggest that Treg cell plays a principal role in the immune response among Yusho patients.

The Yusho poisoning incident, caused by rice oil contaminated with polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs), and polychlorinated dibenzofurans (PCDFs) generated by heat-denatured PCBs, occurred in 1968 in western Japan. Although severe symptoms are rarely observed today, the levels of PCBs and PCDFs in the sera of Yusho patients remain high. The aryl hydrocarbon receptor (AhR), which also acts as a dioxin receptor, is a transcriptional regulator that mediates dioxin toxicity. Recent studies show that dioxin mediates its immune toxic effects via AhR and that AhR activation induces dysregulation of interleukin (IL)-17-producing T (TH17) cells. This study therefore hypothesized that Yusho patients would show dysregulated TH17 cell-mediated immune responses. To validate the hypothesis, levels of IL-17 and IL-22, each secreted by TH17 cells, along with IL-1β and IL-23 were measured in serum samples from 40 Yusho patients and 40 age-matched controls. Levels of tumor necrosis factor (TNF)-α potentially secreted by TH17 cell-stimulated neutrophils and macrophages were also measured. The results indicated that serum IL-17 levels, as well as those of IL-1β, IL-23, and TNFα, were significantly higher in Yusho patients than in controls. In contrast, serum IL-22 levels were significantly lower in the Yusho patients. These results suggest that Yusho patients have dysregulated TH17 cell-mediated immune responses that may be linked to inflammation., Journal of Immunotoxicology, 11(3), pp.246-249; 2014

強皮症は全身臓器の硬化を特徴とするが，消化管の硬化により生じる偽性腸閉塞はまれであるとされる。ここにわれわれの経験した本疾患の2症例の治療を中心に報告する。症例1：59歳，女性。1995年頃，びまん型全身性強皮症と診断された。2010年8月下旬より腹痛および下痢症状が出現した。腹部レントゲンおよび腹部CTで明らかな閉塞がないものの腸管の拡張を認めたため，強皮症に合併した偽性腸閉塞と診断した。絶飲食ならびに輸液で症状は改善した。症例2：63歳，女性。2008年にびまん型全身性強皮症と診断された。2010年5月下旬より下痢症状と腹部膨満が出現し次第に増悪してきた。腹部レントゲンおよび腹部CTで腸管の拡張像があり強皮症に合併した偽性腸閉塞と診断した。絶飲食と輸液で改善したが，シクロフォスファミドのパルス療法も加えて施行した。強皮症の消化器症状は患者の約8割にみられるが，偽性腸閉塞はその中でも難治性でまれとされる。本症例ならびに文献的考察から，本症例のごとく難治性の場合は，入院の上，絶飲食と輸液を行うことが第一と考えられた。

Systemic sclerosis (SSc) is characterized by immunological abnormalities, especially the production of autoantibodies against various cellular components. Treatment with histone deacetylase (HDAC) inhibitors prevents collagen accumulation in a mouse SSc model. Additionally, autoantibody against HDAC-3 is produced in colon cancer patients, while HDAC-1 and HDAC-2 do not elicit autoantibody response. To determine the presence and levels of antibodies (Abs) against HDAC-3 in SSc. Anti-HDAC-3 Ab was examined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting using human recombinant HDAC-3. The HDAC-3 activity was evaluated by ELISA using the fluorimetric HDAC lysyl substrate that comprises an acetylated lysine side chain. Contrary to our hypothesis that autoimmune background in SSc induced the production of autoantibody against HDACs, IgG and IgM anti-HDAC-3 Ab levels in SSc patients were significantly lower than in normal controls (p < 0.0005 and 0.001, respectively). Furthermore, decreased levels of IgG anti-HDAC-3 Ab were specific to SSc, since IgG anti-HDAC-3 Ab levels in patients with dermatomyositis (DM) and those with systemic lupus erythematosus (SLE) were similar and slightly increased relative to normal controls, respectively. Immunoblotting analysis showed that anti-HDAC-3 Ab was detected in normal controls and patients with DM or SLE, while it was absent in SSc patients. The HDAC-3 activity was significantly inhibited by IgG isolated from sera of normal controls, whereas such inhibitory effect was not observed by IgG isolated from sera of SSc patients. These results indicate the lack of anti-HDAC-3 autoantibody in SSc patients, which is produced in healthy individuals as well as DM and SLE patients, suggesting that this autoantibody might function as protective Ab., This is an electronic version of an article published in Free Radical Research, 42(11-12), 957-965: 2008 November. Free Radical Research is available online at: http://informahealthcare.com/doi/abs/10.1080/08916930802406300, Autoimmunity, 42(2), pp.120-125; 2009

11歳の男児。初診1年程前より両前腕·両下腿を中心とした四肢遠位部に対称性の皮膚硬化が出現した。7ヵ月程前より手関節屈曲，足関節伸展が困難となり，次第に皮膚硬化の範囲が拡大したため当科を受診した。手指および足趾の皮膚硬化はなく，またレイノー症状や爪上皮出血点も認めなかった。血液検査では末梢血中の好酸球の上昇，高γグロブリン血症が認められた。抗核抗体，抗トポイソメラーゼI抗体，抗セントロメア抗体など自己抗体は陰性であった。前腕からの皮膚生検では，筋膜が肥厚し中程度の炎症細胞浸潤を伴っていた。以上より好酸球性筋膜炎と診断した。プレドニゾロンの内服を25mg/日より開始し，速やかに四肢の皮膚硬化は改善した。しかしながら，手指関節・足関節の拘縮は難治であった。手指·足関節拘縮に対してリハビリテーションを開始したが症状の改善に時間を要した。小児発症の好酸球性筋膜炎は稀であるため診断までに時間を要する可能性があり，注意が必要であると考えられた。

2005年から2006年にかけて，当科では若年性全身性強皮症3例を経験した。症例1:15歳，女性。初診の4ヵ月前よりレイノー症状が出現，1ヵ月前より両手指と両手背の皮膚硬化を伴ったため当科を受診した。精査の結果，抗トポイソメラーゼI抗体陽性の全身性強皮症と診断した。肺病変や腎病変など内臓病変の合併は見られなかった。プレドニゾロン(prednisolone;PSL)20mg/dayの投与を行い，皮膚硬化は改善した。症例2:17歳，女性。初診の4年程前よりレイノー症状を認め，1年程前には両手指と両手背の皮膚硬化を自覚した。精査の結果，抗トポイソメラーゼI抗体陽性の全身背強皮症と診断した。逆流性食道炎を認めたが，他の内臓病変の合併は見られなかった。PSL 20mg/dayの投与にて皮膚硬化は改善し，逆流性食道炎もプロトンポンプインヒビターとクエン酸モサプリドの内服にて軽快した。症例3:13歳，女性。初診の4年程前よりレイノー症状が出現し，1年程前に両手指から上腕にかけての皮膚硬化が出現した。精査の結果，抗トポイソメラーゼI抗体陽性の全身性強皮症と診断した。胸焼けを認めたものの，明らかな内臓病変はみられなかった。PSL 20mg/dayの投与にて皮膚硬化は改善した。消化器症状もH2 blockerとクエン酸モサプリドの内服で軽快した。小児発症の全身性強皮症では抗トポイソメラーゼI抗体の陽性例が多いが，重篤な内臓病変の合併は少ないとされている。しかしながら，観察期間が短い報告が多く重篤例も散見されるため，臨床的特徴を明確にするには更なる症例検討が必要である。

Docetaxel and paclitaxel are widely used in the treatment of various malignant neoplasms. Taxane-induced sclerosis is dose-dependent and usually not generalized. Little information on the pathogenesis of scleroderma is currently available. Here, we report a case of generalized scleroderma and a case of early-stage oedematous sclerosis, both of which presented with intense versican deposits after administration of taxane for angiosarcoma.

Aryl hydrocarbon receptor (AhR), recognized as a dioxin receptor, is expressed on the surface of helper T (Th) 17 cells. As PCBs and PCDFs are still detected in the sera of the Yusho patients, we hypothesized dysregulation of Th17 cells in the Yusho patients. In the present study, we measured IL-21 and TGF-beta in the Yusho patients which induce differentiation from Th0 to Th17 cells. Serum levels of IL-21 were lower than those of controls (p < 0.05). Meanwhile, serum levels of TGF-beta were decreased relative to controls, but not significant. These results may imply differentiation from Th0 cells to Th17 cells is not induced in the Yusho patients., 福岡医学雑誌, 104(4), pp.88-90; 2013

We thought that dioxin and dioxin-like compound receptor AhR expressed on the surface of regulatory T (Treg) cells and Th17 cells could regulate immunological functions in the Yusho patients. In the present study, we measured Treg cell related cytokines IL-10 and IL-35 in the Yusho patients. Serum levels of IL-10 were higher, but not significant (p = 0.06), and serum levels of IL-35 were increased (p = 0.006) in comparison with healthy controls. These results imply Treg cell activation in the Yusho patients.

We herein present the case of a 28-day-old female with Japanese spotted fever, who is the youngest reported patient so far. Tick-borne diseases, including Japanese spotted fever, should be included in the differential diagnosis of eruptive fever even in neonates because a treatment delay can lead to a fatal outcome.

CD163 is a 130-kDa, type I transmembrane protein belonging to group B of the cysteine-rich scavenger receptor family. Expression of CD163 is constitutive and/or induced by some stimuli on circulating monocytes and most tissue macrophages. An approximately 130-kDa soluble form of human CD163 is released from the cell surface by proteolysis after oxidative stress or inflammatory stimuli. Thus, an elevated level of circulating soluble CD163 (sCD163) has been reported in diabetes mellitus, which is one of the oxidative conditions. We have already acknowledged that scleroderma (SSc) is one of the oxidative conditions. Therefore, we conducted the measurement of serum sCD163 in SSc patients. After receiving the informed consents, 56 SSc patients were examined; 20 dermatomyositis patients were used as disease controls and 40 persons were used as healthy controls. Blood samples were collected, and the concentration of serum sCD163 was measured by ELISA (human CD163, R&D Systems). Other parameters in the blood of SSc patients were also examined. Statistical analyses were performed using Mann-Whitney U test, and the relationship between parameters was statistically examined by Spearman's rank test. Serum sCD163 levels were elevated in SSc patients compared with normal controls (p< 0.01), with similar levels between limited SSc and diffuse SSc patients. SSc patients with pulmonary fibrosis had increased serum levels of sCD163 than those without pulmonary fibrosis (p, Clinical Rheumatology, 31(7), pp.1059-1064; 2012

Background Systemic sclerosis (SSc) is connective tissue disease characterized by fibrosis and vascular changes in the skin and internal organs with autoimmune background. However, the mechanism is still unknown. Recently, it is reported that cellular senescence is associated with fibrosis and its amelioration in several diseases. Senescence associated β-galactosidase (SA-β-gal) is one of the histological marker for the cellular senescence. Objectives To determine association of cellar senescence in SSc skin and fibroblast. Methods SA-β-gal expression was investigated in skin samples from SSc patients and age- and sex- matched healthy control. SA-β-gal activity was also compared in SSc patients between sclerosis lesion (forearm) and non-sclerotic lesion (upper arm). In addition, SA-β-gal expression was also investigated in fibroblasts from SSc patients and healthy control. Senescent fibroblast established by successive subculture was used for SA-β-gal staining control. Results Senescence fibroblast showed large-scaled shape and nucleus with SA-β-gal staining. SA-β-gal expression was higher in SSc skin than control. SA-β-gal activity was observed mainly in upper dermis. Furthermore, SA-β-gal expression was observed in sclerotic skin lesion of SSc patients, however, its expression was not detected in non-sclerotic lesion of SSc patients. Furthermore, fibroblast from SSc patients showed higher SA-β-gal expression than control fibroblast. Conclusions These results suggest that cellular senescence in SSc fibroblast may contribute to disease development in patients with SSc References Coppe, J.P., et al., Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol, 2008. 6(12): p. 2853-68. Jun, J.I. and L.F. Lau, Cellular senescence controls fibrosis in wound healing. Aging (Albany NY), 2010. 2(9): p. 627-31. Leontieva, O.V. and M.V. Blagosklonny, DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence. Aging (Albany NY), 2010. 2(12): p. 924-35. Frippiat, C., et al., Subcytotoxic H2O2 stress triggers a release of transforming growth factor-beta 1, which induces biomarkers of cellular senescence of human diploid fibroblasts. J Biol Chem, 2001. 276(4): p. 2531-7. Disclosure of Interest None Declared